JOURNAL OF CLINICAL MICROBIOLOGY, Oct. 2010, p. 3762–3764 Vol. 48, No. 10 0095-1137/10/$12.00 doi:10.1128/JCM.00595-10 Copyright ? 2010, American Society for Microbiology. All Rights Reserved.
Bordetella holmesii Bacteremia in Asplenic Children: Report of Four
Cases Initially Misidenti？ed as Acinetobacter lwof;i
11,2334Markos Ioannis Panagopoulos,Maude Saint Jean,Delphine Brun,Nicole Guiso,Sadjia Bekal, 11Philippe Ovetchkine,and Bruce Tapiero*
1Division of Infectious Diseases, Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Montreal, Canada; 2Department of Microbiology and Immunology, CHU Sainte-Justine, University of Montreal, Montreal, Canada; 3Institut Pasteur, French National Reference Center for Pertussis and other Bordetelloses, Paris, France; and 4Quebec Laboratory of Public Health, Sainte-Anne-de Bellevue, Quebec, Canada
Received 21 March 2010/Returned for modi？cation 5 May 2010/Accepted 16 July 2010
Bordetella holmesii is a fastidious Gram-negative rod that was initially identi；ed in 1995. It causes bacter-
emia, predominantly among patients with anatomical or functional asplenia. We report four cases of B.
holmesii bacteremia in asplenic children occurring within the last 4 years. In all cases, B. holmesii was misidenti；ed by an automated system as Acinetobacter lwof;i.
Four male adolescent patients, aged between 13 and 17 tion con？dence level) for all isolates. Some basic characteris- tics did not match this result. A. lwof;i usually grows well on years, presented with mild febrile illness but no other clinically MacConkey agar, has a positive catalase activity, and does not signi？cant complaints within a period of 3.5 years. Three were produce any pigment. All isolates were subsequently identi？ed suffering from sickle cell disease; two of them had undergone splenectomy. In the fourth patient, elective splenectomy was as Bordetella holmesii by 16S rRNA gene sequence analysis performed at Quebec’s Laboratory of Public Health, as previ- performed for an autoimmune hemolytic anemia. No epide- ously described (2). miological link was found between the four patients. At the emergency department, they appeared well and had MICs determined by Etest on Mueller-Hinton agar were no remarkable ？ndings on physical examination or initial lab- 0.25 g/ml for piperacillin, ticarcillin-clavulanate, ceftazi- oratory workup. Blood cultures all grew Gram-negative bacilli. dime, meropenem, cipro，oxacin, trimethoprim-sulfamethox- Two of the patients received intravenous (i.v.) ceftriaxone for azole, and polymixin E; MICs for gentamicin and tobramycin 2 and 7 days, respectively. The remaining patients were treated were 2 g/ml for one isolate and 0.25 g/ml for the remain- with i.v. ceftriaxone followed by oral cipro，oxacin for a total of ing three. Although all patients were treated with ceftriaxone, susceptibility testing for ceftriaxone was not performed. 10 days.
The clinical outcome was uniformly favorable. Clinical and The genus Bordetella belongs to the family of Alcaligenaceae
laboratory ？ndings are summarized in Table 1. and currently comprises eight species, including B. holmesii.
The Gram-negative bacilli isolated from the blood cultures Bordetella pertussis is the causative agent of whooping cough,
(Bactec 9240, Peds Plus, and Plus Aerobic bottles; BD Diag- while Bordetella parapertussis and Bordetella bronchiseptica are
nostics Inc., Sparks, MD) were small and coccoid. They tested also implicated in respiratory tract infections in humans. Bor- negative for catalase, oxidase, nitrate reduction, and urease detella avium is considered a strict avian pathogen but has activity as well as indole spot and oxidative-fermentative (OF) recently been isolated in the sputum of cystic ？brosis patients glucose media. The mean incubation time was 40 h (range, 30 h and others with respiratory disease (9, 19). Bordetella hinzii was to 47.3 h). Colonies grew well at 24 h when inoculated on 5% found to colonize the respiratory tract in poultry and also in humans with cystic ？brosis. It can occasionally cause infection sheep blood agar plates and incubated in 5% CO, whereas 2 in immunocompromised patients (5, 19, 23). Bordetella trema- only three strains showed very limited growth after 48 h on tum has been isolated from ear and wound infections and from MacConkey agar. While they were growing, they all produced a diffusible brown pigment which could have been mistaken for a diabetic patient with a leg ulcer (3, 22). Bordetella petrii has been documented in patients with cystic ？brosis (19), in a alpha-hemolysis on a sheep blood agar plate. We were unable patient with mandibular osteomyelitis, and in another with to identify the isolates through routine laboratory protocols and inoculation into API 20E and API 20NE strips (bio- mastoiditis (7, 20). It is noteworthy that, in this last patient, the Me?rieux Inc.). We ？nally used the Gram-negative card on a Vitek2 automated system misidenti？ed the organism as Vitek2 automated system (bioMe?rieux Inc.), which reported Pseudomonas ；uorescens. A recently proposed species is Bor- Acinetobacter lwof;i with 99% probability (excellent identi？ca- detella ansorpii, which was ？rst isolated in pus from an epider- mal cyst and was also found to cause bacteremia in an immu- nocompromised patient (6, 10). * Corresponding author. Mailing address: Division of Infectious B. holmesii was ？rst described in 1995 as a cause of septice- Diseases, Department of Pediatrics, CHU Sainte-Justine, University of mia in 15 patients, including at least three children with asple- Montreal, 3175 Coˆte-Sainte-Catherine, Montreal, Quebec H3T 1C5, nia, without any further clinical information (24). The ？rst Canada. Phone: (514) 345-4931, ext. 5566. Fax: (514) 345-4908. E-mail: detailed clinical case report was published later that year with email@example.com. the description of a 12-year-old male who had a history of Published ahead of print on 28 July 2010.
VOL. 48, 2010 NOTES 3763 TABLE 1. Clinical characteristics and laboratory ？ndings for the 4 patients Result for patient: Parameter 1 2 3 4
15 Age (yr) 13 17 13 Medical condition Sickle cell anemia Autoimmune Sickle cell anemia Sickle cell anemia hemolytic anemia Splenectomy Yes No Yes Yes Age at splenectomy (yr) 3 6 4 39.5 Temp (?C, maximum) 39.7 39.5 40 1 Duration of fever (days) 3 3 2 Treatment Ceftriaxone for 2 days Ceftriaxone for 7 days Ceftriaxone for 7 days Ceftriaxone for 5 days followed by cipro，oxacin followed by cipro，oxacin for 3 days for 5 days Blood hemoglobin level (g/dl) 9.7 12.1 9.5 11.7 3Platelet count/mm 321,000 677,000 261,000 396,000 3White blood cell count/mm 5,590 17,280 15,640 11,560 Neutrophils (%) 46 83 81 87 Normal Normal Chest X ray Normal Normal aOther test results Cardiac U/S, normal Tc/Ga scintigraphy, normal Tc/Ga scintigraphy, normal Length of hospital stay Not admitted 7 days 4 days 7 days
a U/S, ultrasound; Tc/Ga, technetium-gallium. splenectomy for an idiopathic thrombocytopenic purpura. He strains possess a capsule or not remains unknown. Neverthe-
less, overwhelming sepsis did not occur in our patients and are presented with fever but had an otherwise-normal physical
not reported in the literature. examination. He quickly responded to i.v. ceftriaxone (11).
The Vitek2 automated system failed to identify B. holmesii Since then, B. holmesii has been reported as a cause of bacter-
because the microorganism is not included in its database. In emia, endocarditis, and pneumonia, mainly in immunocompro-
addition, the system does not consider catalase activity or the mised and, more particularly, in asplenic patients (4, 8, 12, 13,
presence of pigment. A. lwof;i was systematically erroneously 15, 18, 21). In the largest published series so far, describing 26
patients with B. holmesii bacteremia, 85% had anatomical or reported with a high identi？cation con？dence level.
functional asplenia (18). The clinical course usually remained The above-described clinical cases and results of microbio- uneventful, and patients tended to recover without complica- logical analysis support the growing evidence for the role of B.
tions. However, an immunocompetent adolescent with B. holmesii as a pathogen among asplenic patients and suggest holmesii bacteremia and lobar pneumonia developed empy- that it should always be considered, especially when the Vitek2 ema. He eventually evolved toward pulmonary ？brosis (17). In automated system reports A. lwof;i.
most published articles, failure of identi？cation by commercial REFERENCES systems and identi？cation ultimately made possible by using 1. Antila, M., Q. He, C. de Jong, I. Aarts, H. Verbakel, S. Bruisten, S. Keller, 16S rRNA gene sequence analysis are reported. None of the M. Haanpera, J. Makinen, E. Eerola, M. K. Viljanen, J. Mertsola, and A. van der Zee. 2006. Bordetella holmesii DNA is not detected in nasopharyngeal other studies clearly mentioned systematic misidenti？cation as swabs from Finnish and Dutch patients with suspected pertussis. J. Med. A. lwof;i or another bacterium using an automated identi？ca- Microbiol. 55:1043–1051. tion system. 2. Bekal, S., C. Gaudreau, R. A. Laurence, E. Simoneau, and L. Raynal. 2006. Streptococcus pseudoporcinus sp. nov., a novel species isolated from the B. holmesii has been isolated from cultures of nasopharyn- genitourinary tract of women. J. Clin. Microbiol. 44:2584–2586. geal specimens in 0.6% of U.S. patients with pertussis-like 3. Daxboeck, F., E. Goerzer, P. Apfalter, M. Nehr, and R. Krause. 2004. Iso- symptoms (25) but was not demonstrated using B. holmesii- lation of Bordetella trematum from a diabetic leg ulcer. Diabet. Med. 21: 1247–1248. speci？c PCR on nasopharyngeal swabs from Dutch and Finn- 4. Dorbecker, C., C. Licht, F. Korber, G. Plum, C. Haefs, B. Hoppe, and H. ish patients with the same symptoms (1). The role of B. Seifert. 2007. Community-acquired pneumonia due to Bordetella holmesii in holmesii in respiratory tract colonization or infection remains a patient with frequently relapsing nephrotic syndrome. J. Infect. 54:e203– e205. to be elucidated. There is no known reservoir for B. holmesii. 5. Fry, N. K., J. Duncan, M. T. Edwards, R. E. Tilley, D. Chitnavis, R. Harman, Modes of acquisition also remain to be identi？ed. No person- H. Hammerton, and L. Dainton. 2007. A UK clinical isolate of Bordetella hinzii from a patient with myelodysplastic syndrome. J. Med. Microbiol. to-person transmission has been described to date. B. holmesii 56:1700–1703. reacts as an opportunistic pathogen with low virulence that 6. Fry, N. K., J. Duncan, H. Malnick, and P. M. Cockcroft. 2007. The ？rst UK tends to cause usually uncomplicated and often self-limited isolate of ‘Bordetella ansorpii’ from an immunocompromised patient. J. Med. Microbiol. 56:993–995. infection, such as that seen in our patients. 7. Fry, N. K., J. Duncan, H. Malnick, M. Warner, A. J. Smith, M. S. Jackson, The increased susceptibility to infection and overwhelming and A. Ayoub. 2005. Bordetella petrii clinical isolate. Emerg. Infect. Dis. sepsis, predominantly with encapsulated bacteria, is well rec- 11:1131–1133. 8. Greig, J. R., S. S. Gunda, and J. T. C. Kwan. 2001. Bordetella holmesii ognized in asplenic patients. Sequencing of B. pertussis, B. bacteraemia in an individual on haemodialysis. Scand. J. Infect. Dis. 33:716– parapertussis, and B. bronchiseptica genomes revealed the pres- 717. 9. Harrington, A. T., J. A. Castellanos, T. M. Ziedalski, J. E. Clarridge III, and ence of a locus that is likely to encode a polysaccharide cap- B. T. Cookson. 2009. Isolation of Bordetella avium and novel Bordetella sule, and a recent report demonstrated the presence of a cap- strain from patients with respiratory disease. Emerg. Infect. Dis. 15:72–74. sule on the surface of B. pertussis (14, 16). Whether B. holmesii 10. Ko, K. S., K. R. Peck, W. S. Oh, N. Y. Lee, J. H. Lee, and J. H. Song. 2005.
3764 NOTES J. CLIN. MICROBIOL.
New species of Bordetella, Bordetella ansorpii sp. nov., isolated from the 19. Spilker, T., A. A. Liwienski, and J. J. LiPuma. 2008. Identi？cation of Bor- purulent exudate of an epidermal cyst. J. Clin. Microbiol. 43:2516–2519. detella spp. in respiratory specimens from individuals with cystic ？brosis. 11. Lindquist, S. W., D. J. Weber, M. E. Mangum, D. G. Hollis, and J. Jordan. Clin. Microbiol. Infect. 14:504–506. 1995. Bordetella holmesii sepsis in an asplenic adolescent. Pediatr. Infect. 20. Stark, D., L. A. Riley, J. Harkness, and D. Marriott. 2007. Bordetella petrii Dis. J. 14:813–815. from a clinical sample in Australia: isolation and molecular identi？cation. 12. McCavit, T. L., S. Grube, P. Revell, and C. T. Quinn. 2008. Bordetella J. Med. Microbiol. 56:435–437. holmesii bacteremia in sickle cell disease. Pediatr. Blood Cancer 51:814–816. 21. Tang, Y. W., M. K. Hopkins, C. P. Kolbert, P. A. Hartley, P. J. Severance, 13. Morris, J. T., and M. Myers. 1998. Bacteremia due to Bordetella holmesii. and D. H. Persing. 1998. Bordetella holmesii-like organisms associated with Clin. Infect. Dis. 27:912–913. septicemia, endocarditis, and respiratory failure. Clin. Infect. Dis. 26:389– 14. Neo, Y., R. Li, J. Howe, R. Hoo, A. Pant, S. Ho, and S. Alonso. 2010. Evidence 392. for an intact polysaccharide capsule in Bordetella pertussis. Microbes Infect. 22. Vandamme, P., M. Heyndrickx, M. Vancanneyt, B. Hoste, P. De Vos, E. 12:238–245. Falsen, K. Kersters, and K. H. Hinz. 1996. Bordetella trematum sp. nov., 15. Njamkepo, E., F. Delisle, I. Hagege, G. Gerbaud, and N. Guiso. 2000. Bor- isolated from wounds and ear infections in humans, and reassessment of detella holmesii isolated from a patient with sickle cell anemia: analysis and Alcaligenes denitri;cans Ruger and Tan 1983. Int. J. Syst. Bacteriol. 46:849– comparison with other Bordetella holmesii isolates. Clin. Microbiol. Infect. 858. 6:131–136. 23. Vandamme, P., J. Hommez, M. Vancanneyt, M. Monsieurs, B. Hoste, B. 16. Preston, A., J. Parkhill, and D. J. Maskell. 2004. The bordetellae: lessons Cookson, C. H. Wirsing von Konig, K. Kersters, and P. J. Blackall. 1995. from genomics. Nat. Rev. Microbiol. 2:379–390. Bordetella hinzii sp. nov., isolated from poultry and humans. Int. J. Syst. 17. Russell, F. M., J. M. Davis, M. J. Whipp, P. H. Janssen, P. B. Ward, J. R. Bacteriol. 45:37–45. Vyas, M. Starr, S. M. Sawyer, and N. Curtis. 2001. Severe Bordetella 24. Weyant, R. S., D. G. Hollis, R. E. Weaver, M. F. Amin, A. G. Steigerwalt, S. P. O’Connor, A. M. Whitney, M. I. Daneshvar, C. W. Moss, and D. J. Brenner. holmesii infection in a previously healthy adolescent con？rmed by gene 1995. Bordetella holmesii sp. nov., a new gram-negative species associated sequence analysis. Clin. Infect. Dis. 33:129–130. 18. Shepard, C. W., M. I. Daneshvar, R. M. Kaiser, D. A. Ashford, D. Lonsway, with septicemia. J. Clin. Microbiol. 33:1–7. J. B. Patel, R. E. Morey, J. G. Jordan, R. S. Weyant, and M. Fischer. 2004. 25. Yih, W. K., E. A. Silva, J. Ida, N. Harrington, S. M. Lett. and H. George. 1999. Bordetella holmesii-like organisms isolated from Massachusetts pa- Bordetella holmesii bacteremia: a newly recognized clinical entity among asplenic patients. Clin. Infect. Dis. 38:799–804. tients with pertussis-like symptoms. Emerg. Infect. Dis. 5:441–443.